Identifying Toxicologically Significant Compounds in Urban Wildfire Ash Using In Vitro Bioassays and High-Resolution Mass Spectrometry

Abstract

Urban wildfires may generate numerous unidentified chemicals of toxicity concern. Ash samples were collected from burned residences and from an undeveloped upwind reference site, following the Tubbs fire in Sonoma County, California. The solvent extracts of ash samples were analyzed using GC– and LC–high-resolution mass spectrometry (HRMS) and using a suite of in vitro bioassays for their bioactivity toward nuclear receptors [aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and androgen receptor (AR)], their influence on the expression of genetic markers of stress and inflammation [interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2)], and xenobiotic metabolism [cytochrome P4501A1 (CYP1A1)]. Genetic markers (CYP1A1, IL-8, and COX-2) and AhR activity were significantly higher with wildfire samples than in solvent controls, whereas AR and ER activities generally were unaffected or reduced. The bioassay responses of samples from residential areas were not significantly different from the samples from the reference site despite differing chemical compositions. Suspect and nontarget screening was conducted to identify the chemicals responsible for elevated bioactivity using the multiple streams of HRMS data and open-source data analysis workflows. For the bioassay endpoint with the largest available database of pure compound results (AhR), nontarget features statistically related to whole sample bioassay response using Spearman’s rank-order correlation coefficients or elastic net regression were significantly more likely (by 10 and 15 times, respectively) to be known AhR agonists than the overall population of compounds tentatively identified by nontarget analysis. The findings suggest that a combination of nontarget analysis, in vitro bioassays, and statistical analysis can identify bioactive compounds in complex mixtures.

Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways

“…Our experiment showed that PMFF increased the mRNA expression of IL-6, IL-8, TNF-α, and COX-2 in the treated cells. Consistent with the results of previous studies, PM from wildfire and wood smoke emissions produced high levels of IL-6, IL-8, TNF-α, and COX-2 both in vitro and in vivo [71][72][73]. Our results also demonstrated that RA-RF, a natural polyphenol component found in perilla, reduced IL-6, IL-8, TNF-α, and COX-2 gene expression.…”

Aryl Hydrocarbon Receptor Signaling Synergizes with TLR/NF-κB-Signaling for Induction of IL-22 Through Canonical and Non-Canonical AhR Pathways

“…In recent years studies have shown that the AhR acts as an environmental sensor of environmental pollutants such as ambient air particulate matter (PM) modifying the immune response ( Vogel et al, 2020 ). Especially, PM collected from TRAP and wildfires have been found to activate the AhR pathway and induce CYP1A1 as well as inflammatory cytokines ( Castañeda et al, 2018 ; Young et al, 2021 ; O'Driscoll et al, 2018 ). Here we tested the effects of TRAP-derived PM collected in a tunnel system near San Francisco (CA) before and during a firestorm in 2017 and a PM sample collected from the Carr wildfire in Redding (CA) on the expression of IL-22 in BMM ( Figure 4A ).…”

“…Whereas, the exposure to endogenous ligands like FICZ or the prototypical ligand TCDD may totally depend upon AhR, environmentally abundant AhR ligands in mixtures such as PM containing PAHs and metals may involve additional pathways including NF-κB to dysregulate the expression of cytokines like IL-22. Recently, we were able to identify components in wildfire ash samples which correlated with activation of AhR signaling and the induction of CYP1A1 and IL-8 in macrophages ( Young et al, 2021 ). Wildfire smoke contains numerous hazardous chemicals which may lead to adverse health effects, including potential AhR ligands such as PAHs and dioxin-like chemicals ( Keir et al, 2017 ; Beitel et al, 2020 ).…”

“…Recent reports showed that ambient particulate matter (PM) may contain significant amounts of PAHs, which are a relevant source of environmental AhR ligands ( Vogel et al, 2020 ). Consequently, recent work described a central role of the AhR as a mediator of inflammatory genes induced by air pollution PM and their chemical components generated by traffic and combustion in urban areas or by wildfire smoke ( Castañeda et al, 2018 ; D'Evelyn et al, 2021 ; Dahlem et al, 2020 ; Yuan et al, 2020 ; Young et al, 2021 ). Further, a recent study revealed that PAHs are a critical component in PM promoting T helper 17 (Th17) cell-polarization and secretion of IL-17A from T cells in vivo associated with autoimmune diseases ( O'Driscoll et al, 2018 ).…”

Adapting to Climate Change: Leveraging Systems-Focused Multidisciplinary Research to Promote Resilience

“…SRP researchers have developed and used cutting edge tools to detect contaminants in air, water, and soil, during and after a variety of disasters including Hurricane Florence in North and South Carolina [ 46 , 47 , 48 ], Hurricane Maria in Puerto Rico [ 49 , 50 ], and wildfires [ 51 , 52 ]. They have also documented direct and indirect health effects following hurricanes [ 53 , 54 ].…”